Zenocutuzumab-zbco
Associate Editor(s)-in-Chief: Nehal Eid
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
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Black Box Warning
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TITLEEmbryo-Fetal Toxicity
See full prescribing information for complete Boxed Warning.
Condition Name: (Embryo-Fetal Toxicity: Exposure during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception)
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Overview
Zenocutuzumab-zbco is a HER2-and HER3-directed antibody that is FDA approved for the treatment of It is a bispecific HER2-and HER3-directed antibody indicated for the treatment of: • Adults with advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.* • Adults with advanced, unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.*
- This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).. There is a Black Box Warning for this drug as shown here. Common adverse reactions include • The most common adverse reactions (≥ 10%) in patients were diarrhea musculoskeletal pain, fatigue, nausea, infusion-related reactions (IRR), dyspnea, rash, constipation, vomiting, abdominal pain, and edema..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
• Select patients for treatment with BIZENGRI based on the presence of an NRG1 gene fusion. • Evaluate left ventricular ejection fraction (LVEF) before initiating treatment. • The recommended dosage of BIZENGRI is 750 mg every 2 weeks until disease progression or unacceptable toxicity. • Administer premedications before each infusion to reduce the risk of infusion-related reactions. • Administer as an intravenous infusion, after dilution, over 4 hours.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Zenocutuzumab-zbco in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zenocutuzumab-zbco in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Zenocutuzumab-zbco FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Zenocutuzumab-zbco in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zenocutuzumab-zbco in pediatric patients.
Contraindications
None.
Warnings
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TITLEEmbryo-Fetal Toxicity
See full prescribing information for complete Boxed Warning.
Condition Name: (Embryo-Fetal Toxicity: Exposure during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception)
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• Infusion-Related Reactions(IRR)/Hypersensitivity/Anaphylactic Reactions: Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor for signs and symptoms of IRR. Interrupt infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue it for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis.
• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Permanently discontinue it in patients with ≥ Grade 2 ILD/pneumonitis.
• Left Ventricular Dysfunction: Assess LVEF before initiating treatment and at regular intervals during treatment as clinically indicated. Manage through treatment interruption or discontinuation. Permanently discontinue treatment in patients with symptomatic congestive heart failure (CHF).
Adverse Reactions
Clinical Trials Experience
• The most common adverse reactions (≥ 10%) in patients were diarrhea musculoskeletal pain, fatigue, nausea, infusion-related reactions (IRR), dyspnea, rash, constipation, vomiting, abdominal pain, and edema. • The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were increased GGT, decreased hemoglobin, decreased sodium, decreased platelets, increased AST, increased ALT, increased alkaline phosphatase, decreased magnesium, decreased phosphate, increased aPTT and increased bilirubin.
Postmarketing Experience
To report SUSPECTED ADVERSE REACTIONS, contact Merus N.V. at 1-844-637-8787 (MERUSUS) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
There is limited information regarding Zenocutuzumab-zbco Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
Based on its mechanism of action, it can cause fetal harm when administered to a pregnant woman. There are no available data on the use in pregnant women to inform a drug-associated risk.
Animal studies have demonstrated that HER2 and/or HER3deficiency results in embryo-fetal malformation, including effects on cardiac, vascular and neuronal development, and embryolethality.
Human IgG1 is known to cross the placenta; therefore, it has the potential to be transmitted from the mother to the developing fetus. Advise patients of the potential risk to a
fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Zenocutuzumab-zbco in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Zenocutuzumab-zbco during labor and delivery.
Nursing Mothers
Advise women not to breastfeed during treatment with BIZENGRI and for 2 months after the last dose.
Pediatric Use
The safety and effectiveness of BIZENGRI have not been established in pediatric patients.
Geriatic Use
Of the 175 patients with NRG1 gene fusion positive tumors in the eNRGy study treated with 750 mg every 2 weeks, 75 patients (43%) were 65 years of age or older and 26 patients (15%) were 75 years of age and older. No clinically important differences in safety or efficacy were observed between patients who were ≥65 years of age and younger patients.
Gender
There is no FDA guidance on the use of Zenocutuzumab-zbco with respect to specific gender populations.
Race
There is no FDA guidance on the use of Zenocutuzumab-zbco with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Zenocutuzumab-zbco in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Zenocutuzumab-zbco in patients with hepatic impairment.
Females of Reproductive Potential and Males
It can cause fetal harm when administered to a pregnant woman. Contraception: Advise female patients of reproductive potential to use effective contraception during treatment and for 2 months after the last dose.
Immunocompromised Patients
There is no FDA guidance one the use of Zenocutuzumab-zbco in patients who are immunocompromised.
Administration and Monitoring
Administration
Injection: 375 mg/18.75 mL (20 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial.
Monitoring
There is limited information regarding Zenocutuzumab-zbco Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Zenocutuzumab-zbco and IV administrations.
Overdosage
There is limited information regarding Zenocutuzumab-zbco overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Zenocutuzumab-zbco Pharmacology in the drug label.
Mechanism of Action
Zenocutuzumab-zbco is a bispecific antibody that binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization and preventing NRG1 binding to HER3. Zenocutuzumab-zbco decreased cell proliferation and signaling through the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway. In addition, zenocutuzumab-zbco mediates antibodydependent cellular cytotoxicity (ADCC). Zenocutuzumab-zbco showed antitumor activity in mouse models of NRG1 fusion-positive lung and pancreatic cancers.
Structure
There is limited information regarding Zenocutuzumab-zbco Structure in the drug label.
Pharmacodynamics
The exposure-response relationship and time-course of pharmacodynamic response for zenocutuzumab-zbco have not been fully characterized.
Pharmacokinetics
Zenocutuzumab-zbco pharmacokinetic parameters are expressed as mean unless otherwise specified. Zenocutuzumab-zbco exposure increases proportionally over a dose range from 480 mg (0.6 times the approved recommended dosage) to 900 mg (1.2 times the approved recommended dosage). The median time to steady state of zenocutuzumab-zbco concentrations is 8 weeks and the median accumulation ratio is 1.6-fold at the approved recommended dosage.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
No studies have been performed to assess the carcinogenic or mutagenic potential of zenocutuzumab-zbco.
Animal fertility studies have not been conducted with zenocutuzumab-zbco
Clinical Studies
There is limited information regarding Zenocutuzumab-zbco Clinical Studies in the drug label.
How Supplied
There is limited information regarding Zenocutuzumab-zbco How Supplied in the drug label.
Storage
There is limited information regarding Zenocutuzumab-zbco Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Zenocutuzumab-zbco Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Zenocutuzumab-zbco interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Zenocutuzumab-zbco Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Zenocutuzumab-zbco Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.